Gladstone and Scott: Family, identity, and nation

In the 175 years since his death, Walter Scott has regularly been hailed as an influence by politicians. Amongst the poet-novelist's nineteenth-century political admirers, William Ewart Gladstone was possibly the most ardent, genuine, and significant. Scott's poems and novels were amongst the earliest texts Gladstone read; he read no works (in English), except the Bible, so consistently or completely over such a length of time. They offered him a plethora of inspirations, ideas, and language, which he imbibed and appropriated into his public and private lives. His concept of self, his understanding of family, and his sense of home, were all forged and conducted within a Scottian frame of reference. Scott's life and works also crucially influenced Gladstone's political understanding of the Scottish nation and its people, and his conception of how he could best serve their political interests. This article casts new light on an important and influential relationship in Gladstone's life, establishing that it was neither the superficial and recreational association some have described, nor simply a ploy of an astute politician. The article falls into three parts. The first elucidates how Gladstone's consumption of Scott's writings was seminal in the formation of his private identity, both individual and familial. The second explains how Gladstone's readings of Scott fitted into the specific and serious character of his other reading and knowledge-gathering, and the third shows how the details of Gladstone's response to Scott related to the broader intellectual and cultural context of his public life. By placing Gladstone within his Scottish context, this article shows how frequently and significantly his private and public worlds intersected

Quantum nondemolition measurement of mechanical motion quanta

The fields of opto- and electromechanics have facilitated numerous advances in the areas of precision measurement and sensing, ultimately driving the studies of mechanical systems into the quantum regime. To date, however, the quantization of the mechanical motion and the associated quantum jumps between phonon states remains elusive. For optomechanical systems, the coupling to the environment was shown to preclude the detection of the mechanical mode occupation, unless strong single photon optomechanical coupling is achieved. Here, we propose and analyse an electromechanical setup, which allows to overcome this limitation and resolve the energy levels of a mechanical oscillator. We find that the heating of the membrane, caused by the interaction with the environment and unwanted couplings, can be suppressed for carefully designed electromechanical systems. The results suggest that phonon number measurement is within reach for modern electromechanical setups.Comment: 8 pages, 5 figures plus 24 pages, 11 figures supplemental materia

Effort estimation of FLOSS projects: A study of the Linux kernel

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 SpringerEmpirical research on Free/Libre/Open Source Software (FLOSS) has shown that developers tend to cluster around two main roles: “core” contributors differ from “peripheral” developers in terms of a larger number of responsibilities and a higher productivity pattern. A further, cross-cutting characterization of developers could be achieved by associating developers with “time slots”, and different patterns of activity and effort could be associated to such slots. Such analysis, if replicated, could be used not only to compare different FLOSS communities, and to evaluate their stability and maturity, but also to determine within projects, how the effort is distributed in a given period, and to estimate future needs with respect to key points in the software life-cycle (e.g., major releases). This study analyses the activity patterns within the Linux kernel project, at first focusing on the overall distribution of effort and activity within weeks and days; then, dividing each day into three 8-hour time slots, and focusing on effort and activity around major releases. Such analyses have the objective of evaluating effort, productivity and types of activity globally and around major releases. They enable a comparison of these releases and patterns of effort and activities with traditional software products and processes, and in turn, the identification of company-driven projects (i.e., working mainly during office hours) among FLOSS endeavors. The results of this research show that, overall, the effort within the Linux kernel community is constant (albeit at different levels) throughout the week, signalling the need of updated estimation models, different from those used in traditional 9am–5pm, Monday to Friday commercial companies. It also becomes evident that the activity before a release is vastly different from after a release, and that the changes show an increase in code complexity in specific time slots (notably in the late night hours), which will later require additional maintenance efforts

Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

<p>Abstract</p> <p>Background</p> <p>Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy.</p> <p>Methods</p> <p>Three month old female mdx mice were exposed to the β₁receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining.</p> <p>Results</p> <p>BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers.</p> <p>Conclusions</p> <p>This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.</p

Atypical disengagement from faces and its modulation by the control of eye fixation in children with Autism Spectrum Disorder

By using the gap overlap task, we investigated disengagement from faces and objects in children (9–17 years old) with and without autism spectrum disorder (ASD) and its neurophysiological correlates. In typically developing (TD) children, faces elicited larger gap effect, an index of attentional engagement, and larger saccade-related event-related potentials (ERPs), compared to objects. In children with ASD, by contrast, neither gap effect nor ERPs differ between faces and objects. Follow-up experiments demonstrated that instructed fixation on the eyes induces larger gap effect for faces in children with ASD, whereas instructed fixation on the mouth can disrupt larger gap effect in TD children. These results suggest a critical role of eye fixation on attentional engagement to faces in both groups

Urinary Extracellular Domain of Neurotrophin Receptor p75 as a Biomarker for Amyotrophic Lateral Sclerosis in a Chinese cohort

To comprehensively assess whether p75ECD in urine could be a candidate biomarker for ALS evaluation. Urine samples were collected from 101 ALS patients, 108 patients with other neurological disease (OND) and 97 healthy controls. 61 ALS patients were followed up with clinical data including ALSFRS-r every 6 to 12 months, 23 ALS patients died and 17 ALS patients lost touch during follow up period. Enzyme-linked immunoassay was employed to determine urine p75ECD concentration. The ALSFRS-r was employed to assess the severity of ALS. The concentration of p75ECD in ALS was significantly higher than that of OND and CTRL (p < 0.001). Additionally, urine p75ECD concentrations in ALS-definite grade patients were significantly higher than that in ALS-probable grade and ALS-possible grade patients (p < 0.001). Higher urine p75ECD concentrations were correlated with increased clinical stage (p = 0.0309); urine p75ECD concentrations and ALSFRS-r were negatively correlated (p = 0.022); and urine p75ECD concentration in the fast-progressing ALS group was significantly higher than that in slow-progression (p = 0.0026). Our finding indicates that urine p75ECD concentration provides additional evidence for patients with clinically suspected ALS, and can be employed to evaluate ALS-severity

Automated operant assessments of Huntington's Disease mouse models

Huntington’s disease (HD) presents clinically with a triad of motor, cognitive, and psychiatric symptoms. Cognitive symptoms often occur early within the disease progression, prior to the onset of motor symptoms, and they are significantly burdensome to people who are affected by HD. In order to determine the suitability of mouse models of HD in recapitulating the human condition, these models must be behaviorally tested and characterized. Operant behavioral testing offers an automated and objective method of behaviorally profiling motor, cognitive, and psychiatric dysfunction in HD mice. Furthermore, operant testing can also be employed to determine any behavioral changes observed after any associated interventions or experimental therapeutics. We here present an overview of the most commonly used operant behavioral tests to dissociate motor, cognitive, and psychiatric aspects of mouse models of HD

Estimates of array and pool-construction variance for planning efficient DNA-pooling genome wide association studies

<p>Abstract</p> <p>Background</p> <p>Until recently, genome-wide association studies (GWAS) have been restricted to research groups with the budget necessary to genotype hundreds, if not thousands, of samples. Replacing individual genotyping with genotyping of DNA pools in Phase I of a GWAS has proven successful, and dramatically altered the financial feasibility of this approach. When conducting a pool-based GWAS, how well SNP allele frequency is estimated from a DNA pool will influence a study's power to detect associations. Here we address how to control the variance in allele frequency estimation when DNAs are pooled, and how to plan and conduct the most efficient well-powered pool-based GWAS.</p> <p>Methods</p> <p>By examining the variation in allele frequency estimation on SNP arrays between and within DNA pools we determine how array variance [var(e_array)] and pool-construction variance [var(e_construction)] contribute to the total variance of allele frequency estimation. This information is useful in deciding whether replicate arrays or replicate pools are most useful in reducing variance. Our analysis is based on 27 DNA pools ranging in size from 74 to 446 individual samples, genotyped on a collective total of 128 Illumina beadarrays: 24 1M-Single, 32 1M-Duo, and 72 660-Quad.</p> <p>Results</p> <p>For all three Illumina SNP array types our estimates of var(e_array) were similar, between 3-4 × 10^-4for normalized data. Var(e_construction) accounted for between 20-40% of pooling variance across 27 pools in normalized data.</p> <p>Conclusions</p> <p>We conclude that relative to var(e_array), var(e_construction) is of less importance in reducing the variance in allele frequency estimation from DNA pools; however, our data suggests that on average it may be more important than previously thought. We have prepared a simple online tool, PoolingPlanner (available at <url>http://www.kchew.ca/PoolingPlanner/</url>), which calculates the effective sample size (ESS) of a DNA pool given a range of replicate array values. ESS can be used in a power calculator to perform pool-adjusted calculations. This allows one to quickly calculate the loss of power associated with a pooling experiment to make an informed decision on whether a pool-based GWAS is worth pursuing.</p

ADH1B Arg47His Polymorphism Is Associated with Esophageal Cancer Risk in High-Incidence Asian Population: Evidence from a Meta-Analysis

with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis.. Heterogeneity among studies and their publication bias were also tested. can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32–78.07). allele

Active microrheology and simultaneous visualization of sheared phospholipid monolayers

Two-dimensional films of surface-active agents—from phospholipids and proteins to nanoparticles and colloids—stabilize fluid interfaces, which are essential to the science, technology and engineering of everyday life. The 2D nature of interfaces present unique challenges and opportunities: coupling between the 2D films and the bulk fluids complicates the measurement of surface dynamic properties, but allows the interfacial microstructure to be directly visualized during deformation. Here we present a novel technique that combines active microrheology with fluorescence microscopy to visualize fluid interfaces as they deform under applied stress, allowing structure and rheology to be correlated on the micron-scale in monolayer films. We show that even simple, single-component lipid monolayers can exhibit viscoelasticity, history dependence, a yield stress and hours-long time scales for elastic recoil and aging. Simultaneous visualization of the monolayer under stress shows that the rich dynamical response results from the cooperative dynamics and deformation of liquid-crystalline domains and their boundaries